Investigations are continuing to modify and apply conceptual models based on mathematical analysis kinetic insulin and glucagon secretion patterns. Models will be used to characterize possible compartments, channels, and stimulator-induced feedback inhibitions involved in islet hormone release. The storage forms of insulin, particularly as they relate to zinc, will be examined. Insulin storage and secretion will be correlated with islet uptake of zinc, zinc entry into granules, existence and nature of zinc-insulin complexes, and the possible secretion of such complexes. Compartmentalization and mobilization of stored insulin will be examined by pulse-chase experiments. Particular emphasis will be placed on the possible existence of heterogenous channels which permit preferential release of old or newly synthesized insulin. Changes in structure of these channels induced with various secretagogous or by perturbation of the synthesis-secretion system will be examined. Studies will be continued to evaluate the role of ions, particularly calcium, on the regulation of insulin and glucagon release from islets. Emphasis will be on the distinct calcium-requiring and calcium-induced inhibition of hormone secretions, as they relate to known islet electrical events. Changes in the above phenomena will be determined in both isolated islets and the in vitro perfused pancreas of the non-obese diabetic Chinese hamster and the diabetic streptozotocinized rat.